Fosinopril is the ester prodrug of an angiotensin converting enzyme (ACE) inhibitor, fosinoprilat. The compound can be used as an antihypertensive agent. Its ability to inhibit ACE and thus lower blood pressure is disclosed in U.S. Pat. No. 4,337,201. The compound (the sodium salt, which is the commonly used drug form) is designated chemically as L-proline 4-cyclohexyl-1-[[[2-methyl-1-(1-oxopropoxy)propoxy](4-phenylbutyl)phosphinyl]acetyl]sodium, trans-, see Formula (I).

The prodrug is converted in vivo into the active component by hydrolysis of the diester sidechain. Fosinopril sodium has a relatively low bulk density, exhibits poor flow characteristics, and adheres to metal surfaces during tableting. Fosinopril has been tableted by a wet granulation process using magnesium stearate as a lubricant material. Tablets produced from such blend have low stability, are moisture sensitive and require the use of a protective package for a useful shelf life.
U.S. Pat. No. 5,006,344 suggests the use of sodium stearyl fumarate or hydrogenated vegetable oil instead of magnesium stearate, to increase the stability of fosinopril tablets. The reference however, does not discuss why the two preferred lubricants are found to be better than magnesium stearate, or suggest other possible lubricants. It has been suggested that the degradation of fosinopril in Mg stearate compositions is due to the effect of the Mg metal ion (Thakur, A. B. et al. Pharm. Res. 10 (6) 800–809 (1993)).
It has now been found that fosinopril sodium tablets comprising glyceryl dibehenate as lubricant have excellent stability. Glyceryl dibehenate has several advantages when used in fosinopril compositions as compared to other lubricants used in prior art compositions. In contrast to salts of fatty acids and fatty acid derivatives including magnesium stearate or sodium stearyl fumarate, glyceryl dibehenate is a neutral and non-metal containing compound.
In contrast to hydrogenated vegatable oil, glyceryl dibehenate is chemically a clearly defined substance and can be obtained with a well defined particle size.